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Quantification of minimal disseminated disease by quantitative polymerase chain reaction and digital polymerase chain reaction for NPM-ALK as a prognostic factor in children with anaplastic large cell lymphoma
Detection of minimal disseminated disease is a validated prognostic factor in ALK-positive anaplastic large cell lymphoma. We previously reported that quantification of minimal disease by quantitative real-time polymerase chain reaction (RQ-PCR) in bone marrow applying a cut-off of 10 copies NPM-ALK...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ferrata Storti Foundation
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395281/ https://www.ncbi.nlm.nih.gov/pubmed/31649129 http://dx.doi.org/10.3324/haematol.2019.232314 |
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author | Damm-Welk, Christine Kutscher, Nina Zimmermann, Martin Attarbaschi, Andishe Schieferstein, Jutta Knörr, Fabian Oschlies, Ilske Klapper, Wolfram Woessmann, Wilhelm |
author_facet | Damm-Welk, Christine Kutscher, Nina Zimmermann, Martin Attarbaschi, Andishe Schieferstein, Jutta Knörr, Fabian Oschlies, Ilske Klapper, Wolfram Woessmann, Wilhelm |
author_sort | Damm-Welk, Christine |
collection | PubMed |
description | Detection of minimal disseminated disease is a validated prognostic factor in ALK-positive anaplastic large cell lymphoma. We previously reported that quantification of minimal disease by quantitative real-time polymerase chain reaction (RQ-PCR) in bone marrow applying a cut-off of 10 copies NPM-ALK/10(4) copies of ABL1 identifies very high-risk patients. In the present study, we aimed to confirm the prognostic value of quantitative minimal disseminated disease evaluation and to validate digital polymerase chain reaction (dPCR) as an alternative method. Among 91 patients whose bone marrow was analyzed by RQ-PCR, more than 10 normalized copy-numbers correlated with stage III/IV disease, mediastinal and visceral organ involvement and low anti-ALK antibody titers. The cumulative incidence of relapses of 18 patients with more than 10 normalized copy-numbers of NPM-ALK was 61±12% compared to 21±5% for the remaining 73 patients (P=0.0002). Results in blood correlated with those in bone marrow (r=0.74) in 70 patients for whom both materials could be tested. Transcripts were quantified by RQ-PCR and dPCR in 75 bone marrow and 57 blood samples. Copy number estimates using dPCR and RQ-PCR correlated in 132 samples (r=0.85). Applying a cut-off of 30 copies NPM-ALK/10(4) copies ABL1 for quantification by dPCR, almost identical groups of patients were separated as those separated by RQ-PCR. In summary, the prognostic impact of quantification of minimal disseminated disease in bone marrow could be confirmed for patients with anaplastic large cell lymphoma. Blood can substitute for bone marrow. Quantification of minimal disease by dPCR provides a promising tool to facilitate harmonization of minimal disease measurement between laboratories and for clinical studies. |
format | Online Article Text |
id | pubmed-7395281 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Ferrata Storti Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-73952812020-08-07 Quantification of minimal disseminated disease by quantitative polymerase chain reaction and digital polymerase chain reaction for NPM-ALK as a prognostic factor in children with anaplastic large cell lymphoma Damm-Welk, Christine Kutscher, Nina Zimmermann, Martin Attarbaschi, Andishe Schieferstein, Jutta Knörr, Fabian Oschlies, Ilske Klapper, Wolfram Woessmann, Wilhelm Haematologica Articles Detection of minimal disseminated disease is a validated prognostic factor in ALK-positive anaplastic large cell lymphoma. We previously reported that quantification of minimal disease by quantitative real-time polymerase chain reaction (RQ-PCR) in bone marrow applying a cut-off of 10 copies NPM-ALK/10(4) copies of ABL1 identifies very high-risk patients. In the present study, we aimed to confirm the prognostic value of quantitative minimal disseminated disease evaluation and to validate digital polymerase chain reaction (dPCR) as an alternative method. Among 91 patients whose bone marrow was analyzed by RQ-PCR, more than 10 normalized copy-numbers correlated with stage III/IV disease, mediastinal and visceral organ involvement and low anti-ALK antibody titers. The cumulative incidence of relapses of 18 patients with more than 10 normalized copy-numbers of NPM-ALK was 61±12% compared to 21±5% for the remaining 73 patients (P=0.0002). Results in blood correlated with those in bone marrow (r=0.74) in 70 patients for whom both materials could be tested. Transcripts were quantified by RQ-PCR and dPCR in 75 bone marrow and 57 blood samples. Copy number estimates using dPCR and RQ-PCR correlated in 132 samples (r=0.85). Applying a cut-off of 30 copies NPM-ALK/10(4) copies ABL1 for quantification by dPCR, almost identical groups of patients were separated as those separated by RQ-PCR. In summary, the prognostic impact of quantification of minimal disseminated disease in bone marrow could be confirmed for patients with anaplastic large cell lymphoma. Blood can substitute for bone marrow. Quantification of minimal disease by dPCR provides a promising tool to facilitate harmonization of minimal disease measurement between laboratories and for clinical studies. Ferrata Storti Foundation 2020-08 /pmc/articles/PMC7395281/ /pubmed/31649129 http://dx.doi.org/10.3324/haematol.2019.232314 Text en Copyright© 2020 Ferrata Storti Foundation Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or internal use. Sharing published material for non-commercial purposes is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for commercial purposes is not allowed without permission in writing from the publisher. |
spellingShingle | Articles Damm-Welk, Christine Kutscher, Nina Zimmermann, Martin Attarbaschi, Andishe Schieferstein, Jutta Knörr, Fabian Oschlies, Ilske Klapper, Wolfram Woessmann, Wilhelm Quantification of minimal disseminated disease by quantitative polymerase chain reaction and digital polymerase chain reaction for NPM-ALK as a prognostic factor in children with anaplastic large cell lymphoma |
title | Quantification of minimal disseminated disease by quantitative polymerase chain reaction and digital polymerase chain reaction for NPM-ALK as a prognostic factor in children with anaplastic large cell lymphoma |
title_full | Quantification of minimal disseminated disease by quantitative polymerase chain reaction and digital polymerase chain reaction for NPM-ALK as a prognostic factor in children with anaplastic large cell lymphoma |
title_fullStr | Quantification of minimal disseminated disease by quantitative polymerase chain reaction and digital polymerase chain reaction for NPM-ALK as a prognostic factor in children with anaplastic large cell lymphoma |
title_full_unstemmed | Quantification of minimal disseminated disease by quantitative polymerase chain reaction and digital polymerase chain reaction for NPM-ALK as a prognostic factor in children with anaplastic large cell lymphoma |
title_short | Quantification of minimal disseminated disease by quantitative polymerase chain reaction and digital polymerase chain reaction for NPM-ALK as a prognostic factor in children with anaplastic large cell lymphoma |
title_sort | quantification of minimal disseminated disease by quantitative polymerase chain reaction and digital polymerase chain reaction for npm-alk as a prognostic factor in children with anaplastic large cell lymphoma |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395281/ https://www.ncbi.nlm.nih.gov/pubmed/31649129 http://dx.doi.org/10.3324/haematol.2019.232314 |
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